title: Design and synthesis of some 3-substituted-2-[(2,4-dichlorophenoxy)-methyl]quinazolin-4(3H)-one derivatives as potential anticonvulsant agents.
abstract: Series of 2,3-disubstituted quinazolinone derivatives and a [1,2,4]triazino[2,3-c]quinazolinone featuring the pharmacophoric elements of anticonvulsant drugs were designed and synthesized. Target compounds were screened for their anticonvulsant activity using the subcutaneous pentylenetetrazole (s.c. PTZ) and maximal electroshock (MES) models. The s.c. PTZ test showed that the most active compound was the amide derivative 9c having a protective dose 50 (PD50) of 200.53 µmol/kg (PD50 of phenobarbitone=62.18 µmol/kg); nevertheless, this low potency is outweighed by the much higher safety profile of 9c (LD50 >3000 mg/kg). In the MES screening, seven compounds were equal to or more active than phenytoin; some of these compounds were less neurotoxic than phenytoin. Few compounds such as 9c and 10 were effective in both models. LD50 for the most active compounds was calculated.
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy Cairo University, Kasr El-Eini, Cairo 11562, Egypt.
authors.forename: Safinaz El-Sayed
authors.initials: Sel-S
authors.lastname: Abbas
authors.forename: Fadi Mohsen
authors.initials: FM
authors.lastname: Awadallah
authors.forename: Nashwa Ahmed
authors.initials: NA
authors.lastname: Ibrahim
authors.forename: Eman Gaber
authors.initials: EG
authors.lastname: Said
authors.forename: Gihan
authors.initials: G
authors.lastname: Kamel
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D004195:Disease Models, Animal; D015195:Drug Design; D005260:Female; D006834:Hydrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects; D010433:Pentylenetetrazole / Q000633:toxicity; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D052999:Quinazolinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy; D014227:Triazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use
chemical_list: C585888:6-(2,4-dichlorophenoxy)methyl-2H-(1,2,4)triazino(2,3-c)quinazolin-3(4H)-one; D000927:Anticonvulsants; D006834:Hydrazines; C585887:N-(2-(2,4-dichlorophenoxy)methyl-4-oxo-4H-quinazolin-3-yl)-2-((N'-pyridine-4-carbonyl)hydrazino)acetamide; D011799:Quinazolines; D052999:Quinazolinones; D014227:Triazines; D010433:Pentylenetetrazole